JPS6337085B2 - - Google Patents
Info
- Publication number
- JPS6337085B2 JPS6337085B2 JP54124593A JP12459379A JPS6337085B2 JP S6337085 B2 JPS6337085 B2 JP S6337085B2 JP 54124593 A JP54124593 A JP 54124593A JP 12459379 A JP12459379 A JP 12459379A JP S6337085 B2 JPS6337085 B2 JP S6337085B2
- Authority
- JP
- Japan
- Prior art keywords
- ginsenoside
- agent according
- antitumor agent
- main component
- antitumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 229930182494 ginsenoside Natural products 0.000 claims description 49
- 229940089161 ginsenoside Drugs 0.000 claims description 45
- 229930182490 saponin Natural products 0.000 claims description 24
- 235000017709 saponins Nutrition 0.000 claims description 24
- 150000007949 saponins Chemical class 0.000 claims description 22
- 239000002246 antineoplastic agent Substances 0.000 claims description 16
- 235000008434 ginseng Nutrition 0.000 claims description 6
- 235000002789 Panax ginseng Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 240000004371 Panax ginseng Species 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 2
- 238000010898 silica gel chromatography Methods 0.000 claims description 2
- 241000196324 Embryophyta Species 0.000 claims 1
- 239000008247 solid mixture Substances 0.000 claims 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 15
- 244000000626 Daucus carota Species 0.000 description 10
- 235000002767 Daucus carota Nutrition 0.000 description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 229930183217 Genin Natural products 0.000 description 4
- -1 diol saponins Chemical class 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- 150000002338 glycosides Chemical class 0.000 description 4
- 241000208340 Araliaceae Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 3
- 235000003140 Panax quinquefolius Nutrition 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PVLHOJXLNBFHDX-XHJPDDKBSA-N Panaxadiol Chemical compound C[C@]1([C@H]2CC[C@@]3([C@@H]2[C@H](O)C[C@H]2[C@]3(CC[C@H]3C(C)(C)[C@@H](O)CC[C@@]32C)C)C)CCCC(C)(C)O1 PVLHOJXLNBFHDX-XHJPDDKBSA-N 0.000 description 2
- SYFJYASKXNAXKC-UHFFFAOYSA-N Panaxadiol Natural products CC1(C)CCCC(O1)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CCC34C SYFJYASKXNAXKC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 229940008396 carrot extract Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 150000002009 diols Chemical group 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000043141 Nuclear RNA Human genes 0.000 description 1
- 108020003217 Nuclear RNA Proteins 0.000 description 1
- 235000002791 Panax Nutrition 0.000 description 1
- 241000208343 Panax Species 0.000 description 1
- QFJUYMMIBFBOJY-UXZRXANASA-N Panaxatriol Chemical compound C[C@]1([C@H]2CC[C@@]3([C@@H]2[C@H](O)C[C@H]2[C@]3(C[C@@H](O)[C@H]3C(C)(C)[C@@H](O)CC[C@@]32C)C)C)CCCC(C)(C)O1 QFJUYMMIBFBOJY-UXZRXANASA-N 0.000 description 1
- VIXIMKLMEZTTTC-UHFFFAOYSA-N Panaxatriol Natural products CC1(C)CCCC(O1)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5C(O)CC34C VIXIMKLMEZTTTC-UHFFFAOYSA-N 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002929 anti-fatigue Effects 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- DOAOYJIOTYDTNV-UHFFFAOYSA-N butan-1-ol;ethyl acetate;hydrate Chemical compound O.CCCCO.CCOC(C)=O DOAOYJIOTYDTNV-UHFFFAOYSA-N 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- OORMXZNMRWBSTK-UHFFFAOYSA-N dammaran Natural products C1CCC(C)(C)C2CCC3(C)C4(C)CCC(C(C)CCCC(C)C)C4CCC3C21C OORMXZNMRWBSTK-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000235 effect on cancer Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- YURJSTAIMNSZAE-HHNZYBFYSA-N ginsenoside Rg1 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YURJSTAIMNSZAE-HHNZYBFYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 150000004072 triols Chemical group 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明はオタネニンジンのサポニンである精製
ギンセノシドからなる抗腫瘍剤に関するものであ
る。さらに詳しくはオタネニンジン（Panax
Ginseng C.A.Meyer）（以下、ニンジンという）
の精製ギンセノシドRg1（以下、単にRg1という）、
またはRg1を主成分とするギンセノシドRg2（以
下、単にRg2という）およびギンセノシドRf（以
下、単にRf1という）の一方まは両方を含有する
抗腫瘍剤と、精製ギンセノシドRb1（以下、単に
Rb1という）、またはRb1を主成分とするギンセノ
シドRb2（以下、単にRb2という）、ギンセノシド
Ra（以下、単にRaという）およびギンセノシドRp
（以下、単にRpという）のいづれかまたは全部を
含有する抗腫瘍剤に関するものである。
該サポニンの生理学的意義および薬理作用等に
ついては多くの研究がなされその広範な薬効は科
学的にも次第に明らかにされつつある（代謝、第
10巻、臨時増刊号、第556頁、1973年）。その内容
をまとめると次の如くである。
ニンジンの薬理学的研究は、いままで粗エキス
の段階で行なわれていたが、十数年前より、柴
田、田中、庄司ら、またソ連のエリアコブ
（Elyakov）らによりサポニンの構造決定が行な
われ、さらに薬理学的有効成分の抽出が行なわ
れ、各サポニンおよびそのゲニンの薬理学的研究
が行なわれている。ブレクマン（Brekhman）ら
はニンジンのメタノール抽出物から６種のグリコ
シド〔パナキソシド（panaxoside）とよばれ、
中性のダンマラン ゲニン（dammaran genin）
を有する。パナキソシドＡ，Ｂ，Ｃは極性の弱
い、糖の少ないグリコシドであり、Ｄ，Ｅ，Ｆは
極性が強く糖を多く含んでいる。前者からトリテ
ルペノイド パナキサジオール（triterpenoid
panaxadiol）、後者からパナキサトリオール
（panaxatriol）が得られている。〕を得て種々の
実験を行なつている。ニンジンのグリコシドは水
抽出エキスより持続的な刺激作用があり、ゲニン
も同程度の効力を示している。トリオール群はジ
オール群より高活性が得られたとマウスの遊泳試
験、網登り試験で報告している。抗警告作用はパ
ナキソシドＣとＦおよびそのゲニンで得られた。
パナキソシドＤ，Ｅ，Ｆはラジオメトリツクサブ
スタンス（radiometricsubstance）に赤血球がさ
らされたとき、強力な防御効果を示す。また、加
来らもニンジンより６個のグリコシド（ギンセノ
シドＢ群、ジオール系サポニン３個、ギンセノシ
ドＧ群、トリオール系サポニン３個）をとりだ
し、その薬理作用を検討している。ある成分は一
過性の血圧下降と心拍数の減少、末梢血流量の増
大を示した。また、モルモツト摘出回腸に対する
AChの収縮に拮抗、抗疲労、条件回避抑制、ラ
イテイング挙動（righingbehavior）抑制を認め
ており、ニンジンサポニンの主作用は中枢抑制で
あるとのべている。各サポニンは１％以下の濃度
ではヒト血球を溶血しない。これに対し難波らは
あるトリオール系サポニンはヒト血球に対し強力
な溶血作用を示すが、ジオール系は溶血防御作用
があると報告している。
また、ニンジン抽出物の癌に対する有効性につ
いては臨床試験の結果が公知である（代謝、第10
巻、臨時増刊号、第601頁、1973年）。
一方、癌および担癌動物に対する生理学的作用
についての結果も公知であるが（上記同文献、第
125頁）、結論として腹水肝癌ラツトの延命効果は
顕著にみられなかつた。
しかしながら上記試験で使用された薬剤≪プロ
スチゾール≫は肝の核RNA合成促進作用を目標
にしたスクリーニングでニンジン抽出物よりある
種の分画を選び出したものであり当初より癌に対
する効果を目標にしていないこと、また、その分
離精製法によればニンジンの総サポニンを含有し
ている可能性が大きくしかもそれ以外の成分が混
入しているものでありいづれにしてもその成分は
明らかでない（上記同文献、第564頁）。
そこで本発明者らは該ニンジンの抗腫瘍活性を
示す有効成分を研究し、先にその有効成分の本体
が該ニンジンの抽出物中に含まれていることを始
めて明らかにした。（第37回日本癌学会総会記事、
第160頁、1978年）
本発明者らは更に研究を進め該総サポニンを公
知の方法（Chem.Pharm.Bull.，22，421，1974，
同22，2407，1974）によるシリカゲルカラムクロ
マト法により各種のギンセノシドに分画し、これ
らの精製したギンセノシドを用いた抗腫瘍試験の
結果から有効成分を明らかにした。その結果、精
製されたギンセノシドのRg1またはRg1を主成分
としたRg2およびRfの一方または両方を含有する
分画（GR―Ａと称す）とRb1またはRb1を主成分
とするRa，Rb2，Rpのいづれかを含有する分画
（GR―Ｄと称す）が粗サポニン（総サポニンと
同じ）には認め得なかつた強力な（粗サポニンに
比べて２倍以上の）抗腫瘍活性を示すことを明ら
かにする事に成功し、本発明に到達したものであ
る。
前記の如く総サポニンを有効成分分画に精製し
ない限り投与量のいかんにかかわらず抗腫瘍活性
は90％までに達しない。また本発明の物質は前記
粗サポニンに該当する≪プロスチゾール≫よりも
強力でしかも広範な種類のガン（後述）に有効で
あることが明らかとなつた。
本発明よる有効成分GR―ＡおよびGR―Ｄは
その含有量に差はあるが、該ニンジンの地上部、
胴部、皮部および毛根の生または乾燥および水蒸
気処理したいわゆる紅参のいづれを原料にしても
製造出来る。また、日本、朝鮮、中国などの産地
を問わない。
上記原料より本発明物質を得るには、公知の方
法で調整された粗サポニンを原料とし、原料サポ
ニンの20倍から100倍量（重量）のシリカゲルを
充填したガラスまたはステンレスのカラムにか
け、クロロホルム―メタノール―水の各種混合比
（例えば65：35：10の下層）の溶媒またはｎ―ブ
タノール―酢酸エチル―水の各種混合比（例えば
４：１：２の上層）の溶媒、またはクロロホルム
―メタノール―酢酸エチル―水の各種混合比（例
えば２：２：４：１の下層）などを用いて展開す
る。上記の分離操作が終つた後、各分画を減圧濃
縮または蒸発乾固し乾燥して各々の粉末を得る。
必要に応じては溶媒を変えてこの操作をりかえす
事により上記有効分画を得るものである。かくし
て得られた分画は公知の方法である薄層クロマト
グラフ法により各分画の成分組成を確認し
（Chem.Pharm.Bull.，22，421，1974）、有効部分
を集めて製品化する（第１図参照）。
第１図はニンジンサポニンの薄層クロマトグラ
フの状態を示したものである。１は粗サポニン、
２はGNS（中性サポニン群）、３はRb混合物、４
はRc、５はRg混合物の展開を示してある。吸着
剤としてシリカゲルを用い、発色はH2SO4によ
つて行なつた。展開溶剤はＡの場合にはｎ―ブタ
ノール：酢酸エチル：水＝15：１：４を用い、ま
たＢの場合にはクロロホルム：メタノール：水
65：35：10を用いた。
次に抗腫瘍活性の強かつたGR―ＡとGR―Ｄ
の成分についてその物性を示す。
The present invention relates to an antitumor agent comprising purified ginsenoside, which is a saponin of Panax ginseng. For more information, see Panax ginseng (Panax)
Ginseng CAMeyer) (hereinafter referred to as ginseng)
Purified ginsenoside R g1 (hereinafter simply referred to as R g1 ),
Alternatively, an antitumor agent containing one or both of ginsenoside R g2 ( hereinafter simply referred to as R g2 ) and ginsenoside R f (hereinafter simply referred to as R f1 ) whose main component is R g1, and purified ginsenoside R b1 (hereinafter simply referred to as R f1); ,simply
( referred to as R b1 ), or ginsenoside R b2 (hereinafter simply referred to as R b2) whose main component is R b1 , ginsenoside
R a (hereinafter simply referred to as R a ) and ginsenoside R p
(hereinafter simply referred to as Rp ). Many studies have been conducted on the physiological significance and pharmacological effects of saponins, and their wide-ranging medicinal effects are gradually becoming clear scientifically (metabolism, pharmacological effects, etc.).
Volume 10, special issue, page 556, 1973). The contents are summarized as follows. Until now, pharmacological research on carrots had been carried out at the crude extract stage, but over a decade ago, the structures of saponins were determined by Shibata, Tanaka, Shoji, and others, as well as by Elyakov in the Soviet Union. Furthermore, pharmacologically active ingredients have been extracted, and pharmacological studies of each saponin and its genin have been conducted. Brekhman et al. extracted six types of glycosides [called panaxosides] from methanol extract of carrots.
Neutral dammaran genin
has. Panaxoside A, B, and C are weakly polar glycosides with low sugar content, while D, E, and F are highly polar and contain high sugar content. From the former, the triterpenoid panaxadiol (triterpenoid
panaxadiol), from which panaxatriol is obtained. ] and are conducting various experiments. Ginseng glycosides have a more lasting stimulating effect than aqueous extracts, and genin has shown similar potency. It has been reported that the triol group had higher activity than the diol group in mouse swimming and net climbing tests. Anti-alarm effects were obtained with panaxoside C and F and their genin.
Panaxoside D, E, and F exhibit strong protective effects when red blood cells are exposed to radiometric substances. Kaku et al. also extracted six glycosides (ginsenoside B group, three diol saponins, ginsenoside G group, and three triol saponins) from carrots and investigated their pharmacological effects. One component showed a transient decrease in blood pressure, decrease in heart rate, and increase in peripheral blood flow. In addition, for the guinea pig isolated ileum,
It has been shown to antagonize ACh contraction, anti-fatigue, inhibit conditioned avoidance, and inhibit righing behavior, and states that the main effect of carrot saponins is central inhibition. Each saponin does not hemolyze human blood cells at concentrations below 1%. On the other hand, Namba et al. reported that certain triol-based saponins have a strong hemolytic effect on human blood cells, while diol-based saponins have a hemolytic protective effect. In addition, the results of clinical trials are known regarding the effectiveness of carrot extract against cancer (metabolism,
Volume, special issue, page 601, 1973). On the other hand, the results regarding the physiological effects on cancer and tumor-bearing animals are also known (said document,
(p. 125), the conclusion was that there was no significant effect on prolonging the survival of ascites liver cancer rats. However, the drug ``prostisol'' used in the above test was selected from a certain fraction of carrot extract in a screening targeting the effect of promoting nuclear RNA synthesis in the liver, and was not originally aimed at having an effect on cancer. Furthermore, according to the separation and purification method, there is a high possibility that it contains the total saponin of carrots, and other components are also mixed in, so the components are not clear in any case (see the same reference as above). , p. 564). Therefore, the present inventors studied the active ingredients of the carrot that exhibit antitumor activity, and revealed for the first time that the active ingredients are contained in the extract of the carrot. (Article from the 37th Annual Meeting of the Japanese Cancer Society,
160, 1978) The present inventors further conducted research and determined the total saponin by a known method (Chem.Pharm.Bull., 22 , 421, 1974).
22 , 2407, 1974), it was fractionated into various ginsenosides using silica gel column chromatography, and the active ingredients were clarified from the results of antitumor tests using these purified ginsenosides. As a result, a fraction (referred to as GR-A) containing one or both of R g2 and R f with R g1 or R g1 as the main component of purified ginsenoside, and a fraction with R b1 or R b1 as the main component were obtained. The fraction containing any of R a , R b2 , and R p (referred to as GR-D) has a strong potency (more than twice that of crude saponin) that cannot be observed in crude saponin (same as total saponin). The present invention was achieved by successfully demonstrating that it exhibits antitumor activity. Unless total saponins are purified into active ingredient fractions as described above, antitumor activity will not reach 90% regardless of the dose. It has also been revealed that the substance of the present invention is more potent than <<prostisol>>, which corresponds to the above-mentioned crude saponin, and is effective against a wide variety of cancers (described later). The active ingredients GR-A and GR-D according to the present invention have different contents, but the above-ground parts of the carrot,
It can be produced using either the trunk, skin, and hair roots of so-called red ginseng as raw materials, or dried and steam-treated so-called red ginseng. Also, it does not matter where it is produced, such as Japan, Korea, or China. To obtain the substance of the present invention from the above-mentioned raw materials, crude saponin prepared by a known method is used as a raw material, applied to a glass or stainless steel column packed with silica gel in an amount 20 to 100 times the amount (weight) of the raw material saponin, and then chloroform- Solvents with various mixing ratios of methanol-water (e.g. 65:35:10 lower layer), solvents with various mixing ratios of n-butanol-ethyl acetate-water (e.g. 4:1:2 upper layer), or chloroform-methanol- Develop using various mixing ratios of ethyl acetate and water (for example, lower layer of 2:2:4:1). After the above separation operation is completed, each fraction is concentrated under reduced pressure or evaporated to dryness to obtain each powder.
If necessary, the above-mentioned effective fraction can be obtained by changing the solvent and repeating this operation. The component composition of each fraction thus obtained is confirmed using the well-known method of thin layer chromatography (Chem.Pharm.Bull., 22 , 421, 1974), and the effective parts are collected and manufactured into products. (See Figure 1). FIG. 1 shows the state of a thin layer chromatograph of carrot saponin. 1 is crude saponin,
2 is GNS (neutral saponin group), 3 is R b mixture, 4
shows the evolution of the R c and 5 R g mixtures. Silica gel was used as an adsorbent, and color development was performed using H 2 SO 4 . In case of A, n-butanol:ethyl acetate:water = 15:1:4 was used as the developing solvent, and in case of B, chloroform:methanol:water was used.
65:35:10 was used. Next, GR-A and GR-D have strong antitumor activity.
The physical properties of the components are shown below.
【表】
これらの化学構造式は次の如くである（第２図
参照）。
ギンセノシド Rx
GR―Ａ……（
（
（
（
（
（
（
（
（
（
（
（Rf
Rg1
Rg2
Ｒ＝Ｄ−Glcβ（１→２）Ｄ−Glc
R′＝Ｈ
Ｒ＝Ｄ−Glc
R′＝Ｄ−Glc
Ｒ＝Ｌ−Rhaα（１→２）Ｄ−Glc
R′＝Ｈ
R′＝Ｈ
（20S）―プロトバナキサトリオール類 第２図上
段の式
GR−Ｄ……（
（
（
（
（
（
（
（
（
（
（
（
（Rb1
Rb2
Rp
Ｒ＝Ｄ−Glcβ（１→２）Ｄ−Glc
R′＝Ｄ−Glcβ（１→６）Ｄ−Glc
Ｒ＝Ｄ−Glcβ（１→２）Ｄ−Glc
R′＝Ｌ−Ara（pyr）α（１→６）Ｄ−Glc
（20S）−プロトバナキサジオール類
Ｒ＝Ｄ−Glcβ（１→２）
グルクロニツクアシツド
R′＝Ｄ−Glc
第２図中段の式
第２図下段の式
Raは第１図のAlの薄層クロマトグラフ展開図
に示されているようにRpとRbの中間に表わされ
る成分である。その化学構造は未定であるが、各
種ギンセノシドの分離の過程で他の類似構造のも
のとともに集まり、H2SO4によつて他のギンセ
ノシドと極めて類似した赤紫色に発色し、また例
えば日本薬学会発行、“ケミカル・アンド・フア
ーマシユーテイカル・ビユレテイン”、第22巻、
No.２、1974年２月、第421〜428頁にも示されてい
るように従来からよく知られているギンセノシド
成分である。
本発明の抗腫瘍剤の主成分であるギンセノシド
Rg1およびRb1と本物質の原料であるニンジン根
と葉の総サポニンのマウスにおける急性毒性値を
第２表に示した。[Table] Their chemical structural formulas are as follows (see Figure 2). Ginsenoside R x GR - A ... =D-Glc R=L-R ha α(1→2)D-Glc R'=H R'=H (20S)-Protovanaxatriols Formula in the upper row of Figure 2 GR-D...( ( ( ( ( ( ( ( ( ( ( R b1 R b2 R p R=D-Glcβ(1 → 2)D-Glc R′=D-Glcβ(1→6)D-Glc →2) D-Glc R'=L-Ara(pyr)α(1→6) D-Glc (20S)-protovanaxadiols R=D-Glcβ(1→2) Glucuronic acid R' =D-Glc Equation in the middle row of Figure 2 Equation in the lower row of Figure 2 R a is a component expressed between R p and R b as shown in the thin layer chromatographic development diagram of Al in Figure 1. Its chemical structure is undetermined, but in the process of separating various ginsenosides, it gathers together with other similar structures, and when exposed to H 2 SO 4 it develops a reddish-purple color that is very similar to other ginsenosides. Published by the Pharmaceutical Society of Japan, “Chemical and Pharmaceutical Research,” Volume 22,
No. 2, February 1974, pages 421-428, it is a well-known ginsenoside component. Ginsenoside, the main component of the antitumor agent of the present invention
Table 2 shows the acute toxicity values in mice of R g1 and R b1 and the total saponin of carrot roots and leaves, which are the raw materials for this substance.
【表】
ス
腹腔内 1600 1208 345 306
静脈内 396 492 367 299
[Table]
Intraperitoneal 1600 1208 345 306
Intravenous 396 492 367 299
Claims (1)
ンを、各種溶媒によるシリカゲルクロマトグラフ
法によつて分画したことを特徴とするギンセノシ
ドRg1、またはギンセノシドRg1を主成分とする
ギンセノシドRg2およびギンセノシドRfの一方ま
たは両方を含有するギンセノシドおよびギンセノ
シドRb1、またはギンセノシドRb1を主成分とす
るギンセノシドRb2、ギンセノシドRaおよびギン
セノシドRpのいずれかまたは全部を含有するギ
ンセノシドからなる群から選ばれた抗腫瘍剤。 ２ ギンセノシドRg1からなる特許請求の範囲第
１項に記載の抗腫瘍剤。 ３ ギンセノシドRg1を主成分とし、ギンセノシ
ドRg2をも含有する特許請求の範囲第１項に記載
の抗腫瘍剤。 ４ ギンセノシドRg1を主成分とし、ギンセノシ
ドRfをも含有する特許請求の範囲第１項に記載
の抗腫瘍剤。 ５ ギンセノシドRg1を主成分とし、ギンセノシ
ドRg2およびギンセノシドRfをも含有する特許請
求の範囲第１項に記載の抗腫瘍剤。 ６ ギンセノシドRb1からなる特許請求の範囲第
１項に記載の抗腫瘍剤。 ７ ギンセノシドRb1を主成分とし、ギンセノシ
ドRb2をも含有する特許請求の範囲第１項に記載
の抗腫瘍剤。 ８ ギンセノシドRb1を主成分とし、ギンセノシ
ドRaをも含有する特許請求の範囲第１項に記載
の抗腫瘍剤。 ９ ギンセノシドRb1を主成分とし、ギンセノシ
ドRb2およびギンセノシドRaをも含有する特許請
求の範囲第１項に記載の抗腫瘍剤。 １０ ギンセノシドRb1を主成分とし、ギンセノ
シドRb2、ギンセノシドRaおよびギンセノシドRp
をも含有する特許請求の範囲第１項に記載の抗腫
瘍剤。 １１ 溶液の形態にある特許請求の範囲第１項ま
たは第２〜１０項のいずれかに記載の抗腫瘍剤。 １２ 固体組成物の形態にある特許請求の範囲第
１項または第２〜１０項のいずれかに記載の抗腫
瘍剤。 １３ 粉末の形態にある特許請求の範囲第１項ま
たは第２〜１０項のいずれかに記載の抗腫瘍剤。[Scope of Claims] 1. Ginsenoside R g1 , which is obtained by fractionating total saponins obtained from the whole plant of Panax ginseng by silica gel chromatography using various solvents, or a ginsenoside containing ginsenoside R g1 as a main component. Consists of ginsenoside and ginsenoside R b1 containing one or both of R g2 and ginsenoside R f , or ginsenoside R b2 containing ginsenoside R b1 as a main component, ginsenoside containing one or all of ginsenoside R a and ginsenoside R p Antitumor agents selected from the group. 2. The antitumor agent according to claim 1, which comprises ginsenoside R g1 . 3. The antitumor agent according to claim 1, which contains ginsenoside R g1 as a main component and also contains ginsenoside R g2 . 4. The antitumor agent according to claim 1, which contains ginsenoside R g1 as a main component and also contains ginsenoside R f . 5. The antitumor agent according to claim 1, which contains ginsenoside R g1 as a main component and also contains ginsenoside R g2 and ginsenoside R f . 6. The antitumor agent according to claim 1, comprising ginsenoside R b1 . 7. The antitumor agent according to claim 1, which contains ginsenoside R b1 as a main component and also contains ginsenoside R b2 . 8. The antitumor agent according to claim 1, which contains ginsenoside R b1 as a main component and also contains ginsenoside R a . 9. The antitumor agent according to claim 1, which contains ginsenoside R b1 as a main component and also contains ginsenoside R b2 and ginsenoside R a . 10 Ginsenoside R b1 as the main component, ginsenoside R b2 , ginsenoside R a and ginsenoside R p
The antitumor agent according to claim 1, which also contains the following. 11. The antitumor agent according to claim 1 or any one of claims 2 to 10, which is in the form of a solution. 12. The antitumor agent according to claim 1 or any one of claims 2 to 10, which is in the form of a solid composition. 13. The antitumor agent according to claim 1 or any one of claims 2 to 10, which is in the form of a powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12459379A JPS5646817A (en) | 1979-09-27 | 1979-09-27 | Saponin antitumor agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12459379A JPS5646817A (en) | 1979-09-27 | 1979-09-27 | Saponin antitumor agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5646817A JPS5646817A (en) | 1981-04-28 |
| JPS6337085B2 true JPS6337085B2 (en) | 1988-07-22 |
Family
ID=14889285
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12459379A Granted JPS5646817A (en) | 1979-09-27 | 1979-09-27 | Saponin antitumor agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5646817A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0344876U (en) * | 1989-09-12 | 1991-04-25 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6222721A (en) * | 1985-07-24 | 1987-01-30 | Noebia:Kk | Agent for alleviating mutagenesis |
| KR940000234B1 (en) * | 1989-09-04 | 1994-01-12 | 김송배 | Pharmaceutical preparations and methods for producing new anticancer activity |
| DE10158281A1 (en) * | 2001-11-19 | 2003-05-28 | Mediwirk Gmbh | Pharmaceutical preparation comprises ginsenoside enclosed in micro-shell, e.g. liposome, providing targeted and controlled delivery, useful e.g. in treatment of liver tumors, diabetes mellitus or hypertension |
| CN104383290A (en) * | 2014-12-13 | 2015-03-04 | 李菲 | Body resistance supporting medicine for treating early-stage esophageal cancer and preparation method of body resistance supporting medicine |
-
1979
- 1979-09-27 JP JP12459379A patent/JPS5646817A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0344876U (en) * | 1989-09-12 | 1991-04-25 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5646817A (en) | 1981-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Günther et al. | Quantitative determination of triterpenes in extracts and phytopreparations of Centella asiatica (L.) Urban | |
| DE2724947A1 (en) | PROCESS FOR OBTAINING A GINSEN EXTRACT AND PHARMACEUTICAL PREPARATIONS CONTAINING IT | |
| Sabha et al. | Allium ursinum L.: bioassay-guided isolation and identification of a galactolipid and a phytosterol exerting antiaggregatory effects | |
| JPS6352013B2 (en) | ||
| JPS6337085B2 (en) | ||
| Yamahara et al. | Anti-ulcer action of Panax japonicus rhizome | |
| JP2009120518A (en) | Panax notoginseng extract | |
| NAMBA et al. | Hemolytic and its protective activity of ginseng saponins | |
| EP1131061B1 (en) | Agent for lowering prolactin | |
| KR100620107B1 (en) | Method for preparing ginsenoside Rg2 | |
| CN1833692B (en) | False portulaca oleracea extracts, its prepn. and usage | |
| CN104840451A (en) | Effective part of traditional Chinese medicine for treating coronary heart disease and hyperlipidemia, preparation method and method for isolating active components therefrom | |
| CN110507662B (en) | Polygonatum sibiricum steroidal sapogenin and preparation method and application thereof | |
| Levine | Analysis of acetylsalicylic acid and acetylsalicylic acid tablets | |
| Báthori et al. | New minor ecdysteroids from Silene otites (L.) Wib. | |
| Miles et al. | Tumor inhibitors II: constituents and antitumor activity of Sarracenia flava | |
| Neal et al. | Cactus alkaloids X: Isolation of hordenine and N‐methyltyramine from Ariocarpus kotschoubeyanus | |
| CN110590892B (en) | A kind of triterpenoid compound with antitumor activity isolated from waste Trichosanthes fruit pulp and application thereof | |
| US5558866A (en) | Antineoplastic chemotherapeutic of plant origin, having high selectivity and greatly reduced toxicity, and process for the preparation thereof | |
| JPS58131999A (en) | Antitumor agent | |
| KR100678490B1 (en) | Separation method of Panax diol and Panax triol | |
| Knapp et al. | The Non‐Saponifiable Constituents of Lettuce | |
| EP2649991B1 (en) | Extracts and isolated compounds from Euphorbia granulata Forrsk. for treatment of ulcerative colitis | |
| JPH0471080B2 (en) | ||
| KR101237898B1 (en) | A composition having anti-metastatic effect |